In 2012, micro-quakes have started to occur causing small cracks in the earth’s surface. Jackson Curtis (John Cusack) is a writer in Los Angeles who works part time as a limousine driver for Russian billionaire Yuri Karpov. Jackson’s ex-wife Kate (Amanda Peet) and their children Noah and Lily live with her new boyfriend, plastic surgeon and amateur pilot Gordon. Jackson takes Noah and Lily on a camping trip to Yellowstone National Park, where they find their usual camping spot fenced off while government scientists, including Adrian (now a White House science advisor), monitor the situation. While in Yellowstone, Jackson meets Charlie Frost, a radio show host and conspiracy theorist. Charlie supports a theory that suggests the Mayans predicted the world would come to an end in 2012, and claims he has knowledge of the ark project and possesses a map of the arks’ location. Jackson believes he is a rambling drunk and leaves.
Adrian returns to the White House with ominous news – the earth’s temperature rise is accelerating. The evacuation plan is set into motion. Meanwhile, Jackson’s family returns home as cracks begin to develop along the San Andreas Fault in California and earthquakes occur in the San Francisco Bay area. Jackson grows suspicious and rents a private plane to rescue his family. He collects his family and Gordon when the Earth’s crust displacement begins and they escape Los Angeles as it collapses into the Pacific Ocean.
As millions begin dying in apocalyptic earthquakes worldwide, the group flies to Yellowstone to retrieve Charlie’s map. The group narrowly escapes as the Yellowstone Caldera erupts. Charlie, who stayed behind to make a live broadcast of the eruption, is killed by the blast. Realizing the arks are in China, the group lands in Las Vegas, where they meet Yuri, his twin sons, girlfriend Tamara, and pilot Sasha. They join the group and secure a larger plane, the Antonov An-225, to head across the Pacific. Also bound for the arks aboard Air Force One are Anheuser, Adrian, and First Daughter Laura Wilson (Thandie Newton). President Wilson remained in Washington D.C. to address the nation one last time. He is soon killed by a tsunami that sends the USS John F. Kennedy crashing into the White House. With the Vice President dead and the Speaker of the House missing, Anheuser appoints himself acting Commander-in-Chief.
Sasha discovers that the plane doesn’t have enough fuel to get to China, so they have to make a crash landing in the ocean. But as they get near the ground, they discover that they are indeed in China, as the earth’s crust has shifted.
Yuri, who has purchased ark tickets for himself and his sons, deserts the Curtis family, Gordon, and Tamara upon arriving in China. However, the abandoned group is picked up by Nima, a Buddhist monk. Together, they begin sneaking onto an ark through its hydraulics chamber with the help of Nima’s brother Tenzin, a welder for the ark project. In his last moments, Satnam calls Adrian to inform him that a tsunami is engulfing India and heading towards the arks. Learning of this, Anheuser orders the arks be sealed before the boarding process is complete, trapping thousands outside. Adrian manages to convince the other G8 leaders to let the remaining people on board. As the ark’s tailgate is lowered, Gordon is killed when he falls in between the gears, followed by Tenzin’s large electrical power drill. Yuri sacrifices his life to get his two sons on in time, but the obstruction prevents the gate from closing, rendering the ship unable to start its engines. The tsunami arrives and begins to flood the ark, drowning Tamara and setting the ark helplessly adrift. Jackson and Noah work together to free the drill and its cable from the closing mechanism. The gate closes and the crew regains control of the ark, preventing a fatal collision with Mount Everest.
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When the floodwater from the worldwide tsunamis eventually recedes, satellite data shows that Africa rose in relation to sea level, and its Drakensberg mountains are now the highest on the planet. As the arks set sail for the Cape of Good Hope, Jackson reconciles with his family, and Adrian starts a relationship with Laura. The movie ends with a view of the Earth revealing all continents have merged, and are in the shape of the African continent.